912 resultados para HEART-ASSOCIATION


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Purpose of review The aim of this review is to summarize current evidence about the impact of obstructive sleep apnea (OSA) and intermittent hypoxia on dyslipidemia and provide future perspectives in this area. Recent findings Intermittent hypoxia, a hallmark of OSA, induces hyperlipidemia in lean mice. Hyperlipidemia of intermittent hypoxia occurs, at least in part, due to activation of the transcription factor sterol regulatory element-binding protein-1 (SREBP-1) and an important downstream enzyme of triglyceride and phospholipid biosynthesis, stearoyl-CoA desaturase-1. Furthermore, intermittent hypoxia may regulate SREBP-1 and stearoyl-CoA desaturase-1 via the transcription factor hypoxia-inducible factor 1. In contrast, key genes involved in cholesterol biosynthesis, SREBP-2 and 3-hydroxy-3-methylglutaryl- CoA (HMG-CoA) reductase, are unaffected by intermittent hypoxia. In humans, there is no definitive evidence regarding the effect of OSA on dyslipidemia. Several cross-sectional studies suggest that OSA is independently associated with increased levels of total cholesterol, low-density lipoprotein and triglycerides, whereas others report no such relationship. Some nonrandomized and randomized studies show that OSA treatment with continuous positive airway pressure may have a beneficial effect on lipid profile. Summary There is increasing evidence that intermittent hypoxia is independently associated with dyslipidemia. However, the role of OSA in causality of dyslipidemia remains to be established.

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Chagas disease (American trypanosomiasis) is caused by the protozoan parasite Trypanosoma cruzi. Chagas disease following solid-organ transplantation has occurred in Latin America. This report presents the occurrence of Chagas disease despite negative serological tests in both the donor and the recipient, as well as the effectiveness of treatment. A 21-year-old woman from the state of Sao Paulo (Brazil) underwent cadaveric donor liver transplantation in November 2005, due to cirrhosis of autoimmune etiology. Ten months after liver transplantation, she developed signs and symptoms of congestive heart failure (New York Heart Association functional class IV). The echocardiogram, which was normal preoperatively, showed dilated cardiac chambers, depressed left ventricular systolic function (ejection fraction = 35%) and moderate pulmonary hypertension. Clinical investigation discarded ischemic heart disease and autoimmune and other causes for heart failure. Immuno fluorescence (immunoglobulin M and immunoglobulin G) and hemagglutination tests for T cruzi were positive, and abundant T cruzi amastigotes were readily identified in myocardial biopsy specimens. Treatment with benznidazole for 2 months yielded an excellent clinical response. At the moment of submission, the patient remains in functional class I. This case highlighted that more appropriate screening for T cruzi infection is mandatory in potential donors and recipients of solid-organ transplants in regions where Chagas disease is prevalent. Moreover, it stressed that this diagnosis should always be considered in recipients who develop cardiac complications, since negative serological tests do not completely discard the possibility of disease transmission and since good results can be achieved with prompt trypanocidal therapy.

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Methods: We assessed the outcome of 56 patients with Chagas` cardiomyopathy ([31 men]; mean age of 55 years; mean left ventricular ejection fraction [LVEF] 42%) presenting with either sustained ventricular tachycardia (VT) or nonsustained VT (NSVT), before therapy with implantable cardioverter-defibrillator was available at our center. Results: Over a mean follow-up of 38 +/- 16 months (range, 1-61 months), 16 patients (29%) died, 11 due to sudden cardiac death (SCD), and five from progressive heart failure. Survivors and nonsurvivors had comparable baseline characteristics, except for a lower LVEF (46 +/- 7% vs 31 +/- 9%, P < 0.001) and a higher New York Heart Association class (P = 0.003) in those who died during follow-up. Receiver-operator characteristic curve analysis showed that an LVEF cutoff value of 38% had the best accuracy for predicting all-cause mortality and an LVEF cutoff value of 40% had the best accuracy for prediction of SCD. Using the multivariate Cox regression analysis, LVEF < 40% was the only predictor of all-cause mortality (hazard ratio [HR] 12.22, 95% confidence interval [CI] 3.46-43.17, P = 0.0001) and SCD (HR 6.58, 95% CI 1.74-24.88, P = 0.005). Conclusions: Patients with Chagas` cardiomyopathy presenting with either sustained VT or NSVT run a major risk for mortality when had concomitant severe or even moderate LV systolic dysfunction. (PACE 2011; 54-62).

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Sex-associated differences in hypertension have been observed repeatedly in epidemiological studies; however, the mechanisms conferring vascular protection to females are not totally elucidated. Sex-related differences in intracellular Ca(2+) handling or, more specifically, in mechanisms that regulate Ca(2+) entry into vascular smooth muscle cells have been identified as players in sex-related differences in hypertension-associated vascular dysfunction. Recently, new signalling components that regulate Ca(2+) influx, in conditions of intracellular store depletion, were identified: STIM1 (stromal interaction molecule 1), which works as an intracellular Ca(2+) sensor; and Orai1, which is a component of the CRAC (Ca(2+) release-activated Ca(2+)) channels. Together, these proteins reconstitute store-operated Ca(2+) channel function. Disturbances in STIM1/Orai1 signalling have been implicated in pathophysiological conditions, including hypertension. In the present article, we analyse evidence for sex-related differences in Ca(2+) handling and propose a new hypothesis where sex-related differences in STIM/Orai signalling may contribute to hypertension-associated vascular differences between male and female subjects.

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OBJECTIVES We developed a prognostic strategy for quantifying the long-term risk of coronary heart disease (CHD) events in survivors of acute coronary syndromes (ACS). BACKGROUND Strategies for quantifying long-term risk of CHD events have generally been confined to primary prevention settings. The Long-term Intervention with Pravastatin in Ischemic Disease (LIPID) study, which demonstrated that pravastatin reduces CHD events in ACS survivors with a broad range of cholesterol levels, enabled assessment of long-term prognosis in a secondary prevention setting. METHODS Based on outcomes in 8,557 patients in the LIPID study, a multivariate risk factor model was developed for prediction of CHD death or nonfatal myocardial infarction. Prognostic indexes were developed based on the model, and low-, medium-, high- and very high-risk groups were defined by categorizing the prognostic indexes. RESULTS In addition to pravastatin treatment, the independently significant risk factors included: total and high density lipoprotein cholesterol, age, gender, smoking status, qualifying ACS, prior coronary revascularization, diabetes mellitus, hypertension and prior stroke. Pravastatin reduced coronary event rates in each risk level, and the relative risk reduction did not vary significantly between risk levels. The predicted five-year coronary event rates ranged from 5% to 19% for those assigned pravastatin and from 6.4% to 23.6% fur those assigned placebo. CONCLUSIONS Long-term prognosis of ACS survivors varied substantially according to conventional risk factor profile. Pravastatin reduced coronary risk within all risk levels; however, absolute risk remained high in treated patients with unfavorable profiles. Our risk stratification strategy enables identification of ACS survivors who remain at very high risk despite statin therapy. CT Am Coil Cardiol 2001;38:56-63) (C) 2001 by the American College of Cardiology.

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Thiazolidinediones are a new class of drugs for the treatment of type 2 diabetes, and act by improving insulin sensitivity in adipose tissue, liver and skeletal muscle. Rosiglitazone and pioglitazone are registered for use in monotherapy, and in combination with sulfonylureas and metformin. Pioglitazone is also licensed for use in combination with insulin. There is level II evidence that in patients with inadequate glycaemic control both drugs reduce the level of HbA(1c) and fasting plasma glucose (FPG) when used as monotherapy and in combination with sulfonylurea or metformin or insulin; and both drugs increase levels of HDL and LDL and lower free fatty acid levels, but only pioglitazone significantly lowers triglyceride levels. Both drugs lower fasting insulin and C-peptide levels. In monotherapy, they may be slightly less potent at reducing the level of HbA(1c) than sulfonylureas or metformin. The maximal effect of these agents may not be seen for 6-14 weeks after commencement. Both drugs are well tolerated but liver function must be checked at baseline every second month for the first year, and periodically thereafter. The drugs are currently contraindicated in patients with moderate to severe liver dysfunction and alanine aminotransferase levels more than 2.5 times normal, New York Heart Association III-IV cardiac status, pregnancy, lactation and in children. The main side effects include weight gain, oedema, and mild dilutional anaemia.

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A insuficiência cardíaca afecta cerca de 261 mil pessoas em Portugal constituindo um problema de saúde pública. Pretendemos avaliar aspectos associados à recuperação do estado de saúde nesta síndrome, em particular a esperança, o afecto e a felicidade. Recorremos a um estudo longitudinal com 128 indivíduos sintomáticos com má fracção de ejecção do ventrículo esquerdo. Utilizámos um questionário para caracterizar os aspectos sóciodemográficos, clínicos e funcionais, o Kansas City Cardiomiopathy Questionnaire (KCCQ) para avaliar a qualidade de vida, a Subjective Hapiness Scale (SHS) para a felicidade, a HOPE Scale (HOPE) para a esperança e a Positive And Negative Afect Schedule (PANAS) para o afecto. Os questionários de caracterização sócio-demográfica, clínica e funcional, KCCQ e o SHS foram aplicados em três momentos: no internamento, prévio à instituição de terapêutica médica na sua totalidade e ao terceiro e sexto mês após a intervenção médica, na consulta externa. A maioria dos participantes eram homens em classe III da classificação da New York Heart Association com etiologia isquémica. No internamento e antes da terapêutica médica, observámos que a esperança, a felicidade e o afecto se relacionaram com a qualidade de vida, a felicidade e o afecto positivo com a esperança. No período avaliado foram submetidos a: terapia de ressincronização cardíaca (n=52), cardioversor-desfibrilhador implantável (n=44), cirurgia valvular com revascularização do miocárdio (n=14), optimização terapêutica farmacológica (n=10), transplante cardíaco (n=8). Foram significativos os resultados da qualidade de vida, da classificação da New York Heart Association, do exercício físico, da fracção de ejecção do ventrículo esquerdo e das arritmias cardíacas (estrasístoles e taquicardias ventriculares). A felicidade foi preditora da qualidade de vida e da funcionalidade. O afecto negativo foi preditor da satisfação com a insuficiência cardíaca. Concluímos da importância das variáveis positivas a par dos procedimentos médicos no tratamento das pessoas com insuficiência cardíaca. ABSTRACT - Heart failure affects about 261 000 people in Portugal constituting a public health problem. We intend to evaluate aspects of the health recovery in this syndrome, in particular hope, affection and happiness. We used a longitudinal study with 128 symptomatic patients with poor ejection fraction of left ventricle. We used a questionnaire to characterize the socio-demographic, clinical and functional aspects, the Kansas City Cardiomiopathy Questionnaire (KCCQ) to assess the quality of life, the Subjective Happiness Scale (SHS) for happiness, the HOPE Scale (HOPE) for hope and the Positive And Negative Affect Schedule (PANAS) for affection. The questionnaires of sociodemographic, clinical and functional KCCQ and SHS were applied on three occasions: on admission, prior to the execution of medical therapy in its totality and in the third and sixth months after medical intervention in the outpatient. Most of the participants were men in Class III New York Heart Association classification with ischemic etiology. At admission and before medical therapy, we observed that the hope, happiness and affection were related to the quality of life, happiness and positive affect with hope. Over the studied period were submitted to: cardiac resynchronization therapy (n=52), implantable cardioverter-defibrillator (n=44), valvular surgery with coronary artery bypass graft surgery (n=14), optimizing drug therapy (n=10), heart transplant (n=8). The significant results were the quality of life, the New York Heart Association classification, the exercise, the ejection fraction and left ventricular cardiac arrhythmias (ventricular tachycardia and estrasistoles). Happiness was a predictor of quality of life and functionality. The negative affect was a predictor of satisfaction with heart failure. We concluded that the positive variables and the medical procedures were important in treating people with heart failure.

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Vários estudos demonstraram que os doentes com insuficiência cardíaca congestiva (ICC) têm um compromisso da qualidade de vida relacionada com a saúde (QVRS), tendo esta, nos últimos anos, vindo a tornar-se um endpoint primário quando se analisa o impacto do tratamento de situações crónicas como a ICC. Objectivos: Avaliar as propriedades psicométricas da versão portuguesa de um novo instrumento específico para medir a QVRS na ICC em doentes hospitalizados: o Kansas City Cardiomyopathy Questionnaire (KCCQ). População e Métodos: O KCCQ foi aplicado a uma amostra consecutiva de 193 doentes internados por ICC. Destes, 105 repetiram esta avaliação 3 meses após admissão hospitalar, não havendo eventos ocorridos durante este período de tempo. A idade era 64,4± 12,4 anos (entre 21 e 88), com 72,5% a pertencer ao sexo masculino, sendo a ICC de etiologia isquémica em 42%. Resultados: Esta versão do KCCQ foi sujeita a validação estatística semelhante à americana com a avaliação da fidelidade e validade. A fidelidade foi avaliada pela consistência interna dos domínios e dos somatórios, apresentando valores Alpha de Cronbach idênticos nos vários domínios e somatórios ( =0,50 a =0,94). A validade foi analisada pela convergência, pela sensibilidade às diferenças entre grupos e pela sensibilidade à alteração da condição clínica. Avaliou-se a validade convergente de todos os domínios relacionados com funcionalidade, pela relação verificada entre estes e uma medida de funcionalidade, a classificação da New York Heart Association (NYHA), tendo-se verificado correlações significativas (p<0,01), como medida para avaliar a funcionalidade em doentes com ICC. Efectuou-se uma análise de variância entre o domínio limitação física, os somatórios e as classes da NYHA, tendo-se encontrado diferenças estatisticamente significativas (F=23,4; F=36,4; F=37,4; p=0,0001), na capacidade de descriminação da gravidade da condição clínica. Foi realizada uma segunda avaliação em 105 doentes na consulta do 3º mês após a intervenção clínica, tendo-se observado alterações significativas nas médias dos domínios avaliados entre o internamento e a consulta (diferenças de 14,9 a 30,6 numa escala de 0-100), indicando que os domínios avaliados são sensíveis à mudança da condição clínica. A correlação interdimensões da qualidade de vida que compõe este instrumento é moderada, sugerindo dimensões independentes, apoiando a sua estrutura multifactorial e a adequabilidade desta medida para a sua avaliação. Conclusão: O KCCQ é um instrumento válido, sensível à mudança e específico para medir a QVRS numa população portuguesa com miocardiopatia dilatada e ICC. ABSTRACT - Several studies have shown that patients with congestive heart failure (CHF) have a compromised health-related quality of life (HRQL), and this, in recent years, has become a primary endpoint when considering the impact of treatment of chronic conditions such as CHF. Objectives: To evaluate the psychometric properties of the Portuguese version of a new specific instrument to measure HRQL in patients hospitalized for CHF: the Kansas City Cardiomyopathy Questionnaire (KCCQ). Methods: The KCCQ was applied to a sample of 193 consecutive patients hospitalized for CHF. Of these, 105 repeated the assessment 3 months after admission, with no events during this period. Mean age was 64.4±12.4 years (21-88), and 72.5% were 72.5% male. CHF was of ischemic etiology in 42% of cases. Results: This version of the KCCQ was subjected to statistical validation, with assessment of reliability and validity, similar to the American version. Reliability was assessed by the internal consistency of the domains and summary scores, which showed similar values of Cronbach alpha (0.50-0.94). Validity was assessed by convergence, sensitivity to differences between groups and sensitivity to changes in clinical condition. We evaluated the convergent validity of all domains related to functionality, through the relationship between them and a measure of functionality, the New York Heart Association (NYHA) classification. Significant correlations were found (p<0.01) for this measure of functionality in patients with CHF. Analysis of variance between the physical limitation domain, the summary scores and NYHA class was performed and statistically significant differences were found (F=23.4; F=36.4; F=37.4, p=0.0001) in the ability to discriminate severity of clinical condition. A second evaluation was performed on 105 patients at the 3-month follow-up outpatient appointment, and significant changes were observed in the mean scores of the domains assessed between hospital admission and the clinic appointment (differences from 14.9 to 30.6 on a scale of 0-100), indicating that the domains assessed are sensitive to changes in clinical condition. The correlation between dimensions of quality of life in the KCCQ is moderate, suggesting that the dimensions are independent, supporting the multifactorial nature of HRQL and the suitability of this measure for its evaluation. Conclusion: The KCCQ is a valid instrument, sensitive to change and a specific measure of HRQL in a population with dilated cardiomyopathy and CHF.

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Mestrado em Tecnologia de Diagnóstico e Intervenção Cardiovascular. Área de especialização: Intervenção Cardiovascular.

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A Insuficiência Cardíaca (IC), como uma doença crónica, tem vindo a ser alvo de análise devido ao seu impacto, não só a nível económico, mas também a nível da qualidade de vida (QV). Vários estudos demonstram que os doentes com IC apresentam um comprometimento da QV, em várias dimensões. OBJETIVO: Descrever a QV dos doentes com IC do Centro Hospitalar Tâmega e Sousa (CHTS). METODOLOGIA: O estudo é quantitativo, transversal, prospetivo e descritivo. Foi aplicado, entre janeiro a junho de 2012, o Euro Quality of Life Instrument-5D (EQ-5D) para avaliar o estado de saúde (ES) e o Kansas City Cardiomyopathy Questionnaire (KCCQ) para avaliar a QV de 326 doentes com IC, dos quais 226 seguidos na Consulta Externa (77,9% masculinos, idade média 67,5 ±11,6 anos, desvio padrão) e 100 na Clínica de IC (CIC) (73,0% masculinos, idade média 59,0 anos, desvio padrão ±12,7). Foi usada a estatística descritiva, teste t, qui quadrado e a análise da variância. RESULTADOS: Os doentes do género feminino, do grupo etário 75-100 anos, solteiros, divorciados, separados ou viúvos, que não sabem ler nem escrever, sem apoio dos amigos e sem condições económicas mínimas para o tratamento da IC apresentaram pior ES e QV. Os doentes submetidos à terapia de ressincronização cardíaca e às cirurgias valvular e de revascularização tiveram melhor QV. Os doentes com IC de etiologia isquémica e em classe III-IV da New York Heart Association apresentaram pior ES. Nestas classes e com fração de ejeção ≤35% os doentes tiveram pior QV. Os doentes da CIC evidenciaram melhor ES e QV. CONCLUSÕES: A QV dos doentes com IC do CHTS é influenciada pelos fatores pessoais, clínicos e pelo local de intervenção. É fundamental mensurar a QV, na prática clínica, para evidenciar a perceção do ES dos doentes e o impacto da IC na QV.

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Several studies have shown that patients with congestive heart failure (CHF) have a compromised health-related quality of life (HRQL), and this, in recent years, has become a primary endpoint when considering the impact of treatment of chronic conditions such as CHF. OBJECTIVES: To evaluate the psychometric properties of the Portuguese version of a new specific instrument to measure HRQL in patients hospitalized for CHF: the Kansas City Cardiomyopathy Questionnaire (KCCQ). METHODS: The KCCQ was applied to a sample of 193 consecutive patients hospitalized for CHF. Of these, 105 repeated the assessment 3 months after admission, with no events during this period. Mean age was 64.4 +/- 12.4 years (21-88), and 72.5% were 72.5% male. CHF was of ischemic etiology in 4% of cases. RESULTS: This version of the KCCQ was subjected to statistical validation, with assessment of reliability and validity, similar to the American version. Reliability was assessed by the internal consistency of the domains and summary scores, which showed similar values of Cronbach alpha (0.50-0.94). Validity was assessed by convergence, sensitivity to differences between groups and sensitivity to changes in clinical condition. We evaluated the convergent validity of all domains related to functionality, through the relationship between them and a measure of functionality, the New York Heart Association (NYHA) classification. Significant correlations were found (p < 0.01) for this measure of functionality i patients with CHF. Analysis of variance between the physical limitation domain, the summary scores and NYHA class was performed and statistically significant differences were found (F = 23.4; F = 36.4; F = 37.4, p = 0.0001) in the ability to discriminate severity of clinical condition. A second evaluation was performed on 105 patients at the 3-month follow-up outpatient appointment, and significant changes were observed in the mean scores of the domains assessed between hospital admission and the clinic appointment (differences from 14.9 to 30.6 on a scale of 0-100), indicating that the domains assessed are sensitive to changes in clinical condition. The correlation between dimensions of quality of life in the KCCQ is moderate, suggesting that the dimensions are independent, supporting the multifactorial nature of HRQL and the suitability of this measure for its evaluation. CONCLUSION: The KCCQ is a valid instrument, sensitive to change and a specific measure of HRQL in a population with dilated cardiomyopathy and CHF.

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A implantação de piercings corporais tem sido uma prática cada vez mais comum nas últimas décadas, sobretudo entre os mais jovens. No entanto, não se trata de um procedimento inócuo, podendo apresentar complicações tão graves como a endocardite infecciosa, que pode surgir em indivíduos com ou sem cardiopatia de base. Neste artigo relatamos o caso de uma endocardite pós piercing numa jovem com pacemaker definitivo, tendo havido necessidade de intervenção cirúrgica. Fazemos igualmente uma revisão dos casos de endocardite pós piercing descritos na literatura. Agora que as recomendações da American Heart Association para a profilaxia de endocardite infecciosa estão mais restritas, discutimos a necessidade de inclusão dos piercings corporais nos procedimentos a merecerem terapêutica profiláctica nos indivíduos de alto risco.

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OBJECTIVE: To assess the frequency and severity of the anomalous origin of the left coronary artery (ALCA) from the pulmonary artery (PA). DESIGN OF THE STUDY: Prospective study of case series between March 1991 and December 1994. SETTING: Referral-based Paediatric Cardiology Department of a Tertiary Care Center. PATIENTS AND METHODS: Five consecutive patients (pts) with anomalous origin of the LCA from the PA; there were three infants aged 4 months and two children one 8 year and one 9 year old. There were three girls and two boys. All pts had clinical and 2D-echo and Doppler investigation prior to cardiac catheterization (CC). Indication for CC was based in the association of symptoms and signs of myocarditis or dilated cardiomyopathy of acute or subacute onset and electrocardiographic (ECG) signs of ischemia in infants. In older patients (pts) diagnosis was suspected mainly from ECG. During CC in all pts, aortograms and when necessary selective coronary angiograms were performed. Surgical correction was performed in all children. In two pts stress exercise ECG and stress Thallium studies before and after surgery were performed. RESULTS: two pts had "adult" an three had "infantile" type of ALCA from the PA. CC was performed and diagnosis was confirmed at surgery in all cases. In one child, correct diagnosis was made by ECO prior to CC and in one case LCA to PA fistula was suspected on Colour-Doppler study. No complications were attributed to CC. Several types of surgery were performed: reimplantation of the ALCA from the PA to the aorta (three pts); tunnel connection of the aorta to the ALCA via the PA (one pt) and left internal mammary to LCA anastomosis (one pt). Two infants died intraoperatively due to extensive myocardial infarction and poor left ventricular function. All the three survivors are asymptomatic after a mean follow up of 34 months. Two oldest pts are currently in New York Heart Association functional class I with normal ECG and improved myocardial perfusion on Thallium scan despite almost total occlusion of LCA at the site of implantation in the aorta as diagnosed on coronary angiogram. CONCLUSIONS: ALCA from PA is associated with major morbidity and mortality. Diagnosis should be suspected in pts with unexplained myocardial ischemia on ECG and even more if it is associated to clinical signs of dilated cardiomyopathy or myocarditis. Careful assessment on ECO and pulsed Doppler and colour flow mapping should make the diagnosis in most cases. Although surgery can be performed based only on ECO diagnosis, we strongly advise for angiography in all cases as in our experience there are false negative diagnosis by ECO. Preoperative Thallium studies can be useful for the selection of the type of surgery as pts with very little viable myocardium will not survive the establishment of a direct systemic to coronary blood flow and may be candidates for heart transplantation.

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INTRODUCTION: Mitral regurgitation (MR) is the most common valvular disease and has recently become the target of a number of percutaneous approaches. The MitraClip is virtually the only device for which there is considerable experience, with more than 20,000 procedures performed worldwide. OBJECTIVE: To describe our initial experience of the percutaneous treatment of MR with the MitraClip device. METHODS: We describe the first six MitraClip cases performed in this institution (mean age 58.5 ± 13.1 years), with functional MR grade 4+ and New York Heart Association (NYHA) heart failure class III or IV (n=3), with a mean follow-up of 290 ± 145 days. RESULTS: Procedural success (MR ≤ 2+) was 100%. Total procedure time was 115.8 ± 23.7 min, with no in-hospital adverse events and discharge between the fourth and eighth day, and consistent improvement in the six-minute walk test (329.8 ± 98.42 vs. 385.33 ± 106.95 m) and in NYHA class (three patients improved by two NYHA classes). During follow-up there were two deaths, in two of the four patients who had been initially considered for heart transplantation. CONCLUSION: In patients with functional MR the MitraClip procedure is safe, with both a high implantation and immediate in-hospital success rate. A longer follow-up suggests that the clinical benefit decreases or disappears completely in patients with more advanced heart disease, namely those denied transplantation or on the heart transplant waiting list.